Recently, Magic Angle Spinning (MAS) has been combined with high-field high-resolution Nuclear Magnetic Resonance (HR-NMR) to extend the technique to inhomogeneous systems, such as human and animal tissues. The 1 H HR-MAS spectrum of malignant breast cancer tissue shows dramatically increased levels of phosphocholine compared to nonmalignant breast tissue, and it appears likely that other unambiguous markers can be identified for many other pathologies if the signal to noise ratio (SNR) of the HR-MAS probe can be increased sufficiently. HR NMR probes for liquids have very recently become available with cryogenically cooled sample coils that promise to revolutionize the field of NMR owing to their factor-of-four improvement in SNR. Similar improvements in SNR may be possible in HR-MAS. The engineering challenges of developing a cryo-coil HR-MAS probe appear substantial but not insurmountable, and they will be systematically addressed in the proposed research. Preliminary circuit, computational fluid dynamics (CFD), and thermal analyses show that a combination of (1) a novel approach to quad-resonance MAS (1 H-I 3C-2H-I 5N) with all of the critical circuit elements maintained at -35 K, (2) integrating a ceramic dewar into a novel sample spinner design, and (3) cryogenic preamps offers the potential for a factor-of-three increase in SNR in a cryo-coil HR-MAS probe at fields up to 800 MHz. Prior work in our group with cryo-sample CP-MAS probes has established the viability of the proposed approach. This Phase I project will demonstrate feasibility of a dewared MAS spinner design with a high-efficiency quad-resonance cryogenic circuit. NMR experiments will be performed in a 7 T magnet with the sample at room temperature and the circuit at -90 K to validate essential features of the cryogenic system design. Phase II will complete the developments necessary for quad-resonance cryo-coil HR-MAS with pulsed field gradients at fields up to 18.8 T (800 MHz). Initial field testing at an outside institution is expected by the end of Phase II.